The proposed work represents a continuation of a project to identify and characterize compounds that possess the ability to inhibit the synthesis of dextran from sucrose catalyzed by extracellular glucosyltransferases of cariogenic oral streptococci. Periodateoxidized dextran is a potent and specific inhibitor of soluble fractions of the microbial glucosyltransferases but does not inhibit dextran synthesis by cell- or plaque-bound enzyme. The inhibition of soluble glucosyltransferase by partially oxidized dextran is probably caused by interaction of the dialdehyde groups of the specific polysaccharide with amino groups at, or near to, the enzyme binding site and, therefore, the inability of oxidized dextrans to penetrate the dense matrix of plaque or cell associated material may explain the failure of the macromolecular oxidized derivative to inhibit the bound forms of enzyme. Current investigations are, therefore, directed towards the development of similar types of low molecular weight compounds small enough to penetrate dental plaque and specifically inhibit the associated glucosyltransferases.